Critical role of TRPC6 channels in the formation of excitatory synapses

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Abstract

The transient receptor potential canonical (TRPC) channels are Ca2+-permeable, nonselective cation channels with different biological functions, but their roles in brain are largely unknown. Here we report that TRPC6 was localized to excitatory synapses and promoted their formation via a CaMKIV-CREB–dependent pathway. TRPC6 transgenic mice showed enhancement in spine formation, and spatial learning and memory in Morris water maze. These results reveal a previously unknown role of TRPC6 in synaptic and behavioral plasticity.

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Figure 1: TRPC6 was localized to excitatory postsynapses.
Figure 2: TRPC6 promoted the formation of dendritic spines and excitatory synapses via a CaMKIV-CREB–dependent pathway.
Figure 3: TRPC6 transgenic mice showed enhancement in spine density, spatial learning and memory.

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Acknowledgements

We thank J.W. Putney, Jr., T. Gudermann, D.J. Linden, M.E. Greenberg and S.J. Elledge for providing constructs, W.P. Schilling for TRPC1 antibodies and Q. Hu for confocal imaging. This work was supported by grants from KSCX2-YW-R-099 (Chinese Academy of Science), the 973 program (2006CB806600) and projects 30621062, 30711120566, U0632006 from the National Natural Science Foundation of China.

Author information

J.Z. and W.D. conducted the experiments and wrote the manuscript. K.Z. carried out the recording, and Y.T., H.Y. and Y.J. prepared some of the constructs. Y.D. helped with the transgenic mice and Y.W. supervised the project and wrote the manuscript.

Correspondence to Yizheng Wang.

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Supplementary Figures 1–9 and Supplementary Methods (PDF 2521 kb)

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Zhou, J., Du, W., Zhou, K. et al. Critical role of TRPC6 channels in the formation of excitatory synapses. Nat Neurosci 11, 741–743 (2008) doi:10.1038/nn.2127

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